The purpose of this grant application is to integrate a molecular genetics component to a currently funded study of the effects of behavioral and environmental factors on psychological well-being and diagnostic status of African-American (AA) subjects participating in the Family and Community Health Study (FACHS). The biomaterial for the proposed project will be collected from an existing sample of 771 African American families from Iowa and Georgia who were recruited to participate in the Family and Community Health Study (FACHS), all of whom had a child who was 10 to 11 years of age at the time of recruitment into the study in 1997. The data we have already collected from these women and their families provides a rich and extensive longitudinal foundation upon which to build the proposed project. The proposed use of previously validated genetic markers in addition to sensitive measures of context reduces error variance and capitalization on chance, setting the stage for well targeted analyses that extend theoretical models in important new directions. The FACHS sample is particularly valuable because a large body of evidence has accumulated that demonstrates that both genetic (G), gene-environment correlations (rGE) and gene-environment (GxE) interactions are important in influencing vulnerability to a wide variety health-related outcomes including obesity, hypertension and depression. To date, however, these studies have largely focused on populations of northern European ethnicity to the exclusion of other ethnic groups. In addition, the current sample provides an opportunity to examine previously unrecognized resilience factors in the AA population. We propose to identify specific risk and resilience factors for depression and substance. We hypothesize that G, rGE, and GxE interactions comprise a portion of the risk and resiliency factors responsible for altering vulnerability to depression and substance use in these women. To test this hypothesis we will: 1) collect DNA samples from 1076 subjects (primary and secondary care givers with approximately 200 of the secondary care givers being marital partners), 2) conduct genotyping studies of the best validated candidate genes or loci, 3) conduct analyses of the resulting data to identify factors conveying risk or resilience to depression or substance use, and 4) then examine these factors in the context of longitudinal, contextually sensitive, developmental models of depression and substance use. As a direct result of these studies, we will determine specific G, rGE and GxE effects that either confer protection or confer increased risk for depression, substance use and other health related outcomes among AA women.